Finding Adds To Cancer Research

April 16, 2007
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GRAND RAPIDS — Scientists at the Van Andel Research Institute devised a new way to study carbohydrates that are linked to various diseases, and in the process came upon a finding that may lead to early detection of pancreatic cancer.

VARI Scientific Investigator Brian Haab, Ph.D., lead project scientist Songming Chen, Ph.D., and fellow scientists in the institute’s Laboratory of Cancer Immunodiagnostics developed a method that enables them to identify and measure alterations in carbohydrate structures on proteins that are thought to play a role in diseases such as cancer. Their findings are published in the May issue of Nature Methods.

Haab and his colleagues created the new method by modifying and building upon a technology known as antibody microarray technology — a technology Haab helped develop several years ago. He did some of the first antibody microarray work in his postdoctoral research in 1999 and 2000. Since joining VARI in 2000, he and his team have been developing those methods further, he said. Protein and antibody microarray technology are considered the most advantageous technologies for screening complex protein samples.

VARI scientists used the newly devised method to study structural carbohydrates attached to proteins. They uncovered previously unknown changes in the structure of carbohydrates on certain proteins in the blood of pancreatic cancer patients. The new method made it easier for the scientists to look at variations in the structure of carbohydrates on proteins, called protein glycans, and identify the alterations associated with diseased blood samples and those associated with healthy blood samples.

“We compared the carbohydrate structures from the blood of healthy individuals to the blood of cancer patients and found very consistent alterations on particular proteins in the cancer patients,” Haab said.

It was previously known that there were some changes in carbohydrate structures that were associated with various cancers, including pancreatic cancer, but no causal link has yet been proven between those alterations and the development of or progression of cancer, Haab said. His team has been looking primarily at the role of structural carbohydrates in disease progression.

The study took two years and was funded by the Van Andel Foundation and the National Institutes of Health. Haab’s lab has received a grant from the National Cancer Institute to fund a second leg of the study. VARI scientists are now investigating the effectiveness of using the new method as a basis to detect or diagnose pancreatic cancer.

“Previously, no efficient or effective method existed to quantitatively study glycan variation on specific proteins in multiple biological samples,” Haab said. “Early results indicate that the application of this method could lead to the discovery and characterization of carbohydrate structures that are instrumental in the pathology of cancer and other diseases. This is a first and important step in better treatment.”

VARI has applied for a patent on its new method of studying structural carbohydrates and has licensed the intellectual property to GenTel Biosciences of Wisconsin for commercialization. Why GenTel?

“Because it fit into GenTel’s business market, and they thought they could sell it,” Haab said.

Three research technicians in the Laboratory of Cancer Immunodiagnostics contributed to the study: Derek Bergsma, B.S., Tom LaRoche, B.S., and Darren Hamelinck, M.D. In addition, Randall Brand, M.D., associate professor at Evanston Northwestern Healthcare, and Diane Simeone, M.D., associate professor at the University of Michigan, collaborated with VARI scientists on the study.    

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